Cubam
| amnionless homolog (mouse) | |
|---|---|
| Identifiers | |
| Symbol | AMN |
| Alt. symbols | PRO1028 |
| Entrez | 81693 |
| HUGO | 14604 |
| OMIM | 605799 |
| RefSeq | NM_030943 |
| UniProt | Q9BXJ7 |
| Other data | |
| Locus | Chr. 14 q32.32 |
| cubilin (intrinsic factor-cobalamin receptor) | |
|---|---|
| Identifiers | |
| Symbol | CUBN |
| Alt. symbols | MGA1 |
| Entrez | 8029 |
| HUGO | 2548 |
| OMIM | 602997 |
| RefSeq | NM_001081 |
| UniProt | O60494 |
| Other data | |
| Locus | Chr. 10 p12 |
Cubam, is the term used to refer to a multi-ligand receptor located in the terminal ileum, specializing in absorption of vitamin B12. Cubam is essentially composed of amnionless (AMN), and cubilin.[1][2] Cubilin is essential as a cell receptor recognizing the "vitamin B12-intrinsic factor" complex, whereas amnionless is more involved in the receptor mediated endocytosis of the complex.
Clinical significance
Vitamin B12 is an essential water-soluble vitamin, the absorption of which relies on a functional secretion of salivary haptocorrin, functional secretion of gastric intrinsic factor, functional cleavage of the haptocorrin via pancreatic protease, and a functional absorption via the Cubam at terminal ileum. As expected, a defect at any point of the aforementioned list, can cause malabsoption of vitamin B12, and subsequent macrocytic anemia. The most common cause of Vitamin B12 deficiency is deficiency of the intrinsic factor (IF) usually due to atrophic gastritis, which reduces the number of parietal cells secreting intrinsic factor. This can lead to pernicious anemia. However, a rare abnormality of AMN can also cause vitamin B12 anemia; this condition is referred to as "Imerslund-Gräsbeck syndrome (IGS)." Autosomal recessive mutations in both component of Cubam (AMN, and cubilin) is responsible for Imerslund-Gräsbeck syndrome,[3] which manifests as macrocytic, megaloblastic anemia.
Severe vitamin B12 deficiency is most commonly caused by an autoimmune mediated deficiency in intrinsic factor. Rarely, a mutations in the gene CUBN, coding for cubilin, or AMN, coding for amnionless cause an autosomal reccessive form of vitamin B12 deficiency, known as the Imerslund-Gräsbeck_syndrome. Cubilin and amnionless also play a role in renal tubular function. Cubilin is essential for embryonic development in rodents, but appears not to be essential for normal human embryonic development.[4]
References
- ↑ Pedersen, Gitte Albinus; Chakraborty, Souvik; Stinhauser, Amie L.; Traub, Linton M.; Madsen, Mette (2010). "AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2". Traffic 11 (5): 706–20. doi:10.1111/j.1600-0854.2010.01042.x. PMC 2964065. PMID 20088845.
- ↑ Quadros, Edward V. (2010). "Advances in the understanding of cobalamin assimilation and metabolism". British Journal of Haematology 148 (2): 195–204. doi:10.1111/j.1365-2141.2009.07937.x. PMC 2809139. PMID 19832808.
- ↑ Luder, A. S.; Tanner, S. M.; de la Chapelle, A.; Walter, J. H. (2008). "Amnionless (AMN) mutations in Imerslund-Gräsbeck syndrome may be associated with disturbed vitamin B(12) transport into the CNS". Journal of Inherited Metabolic Disease. doi:10.1007/s10545-007-0760-2. PMID 18181028.
- ↑ Storm T, Emma F, Verroust PJ, Hertz JM, Nielsen R, Christensen EI (January 2011). "A patient with cubilin deficiency". N. Engl. J. Med. 364 (1): 89–91. doi:10.1056/NEJMc1009804. PMID 21208123.